Disease/Drug of interest: Bordetella Pertussis - Erythromycin
Motivation and Background:
Figure 1: The B. pertussis bacterium and all its part labeled.
Pertussis, commonly known as Whooping Cough, is a highly infectious respiratory disease caused by the gram-negative bacteria Bordetella pertussis [2]. Pertussis is categorized by uncontrollable, severe, and chronic coughing which can cause breathing problems in those affected [1]. Due to breathing difficulties, someone infected with Pertussis usually needs to take deep breaths which create a “whooping” sound, leading to the household name “Whooping Cough” [1]. Mainly a concern in children, Pertussis rates have declined in children since the invention of its vaccine in the 1940s [3]. Although the vaccine for Pertussis has saved many lives, Pertussis is still a major cause of vaccine-preventable death, with 30 to 50 million cases per year and 195,000 infant (children younger than 1) deaths worldwide [2, 3]. Ninety percent of these cases appear in developing countries where vaccination rates are lower [3]. Furthermore, in recent years, incidences in older populations has significantly rose, leading to many countries adapting booster vaccines for Pertussis [2]. Adults also act as reservoirs for the bacteria to spread and attack younger children, who are more susceptible to serious side effects of Pertussis, including death [3]. The elderly population also has a 30% fatality rate after being hospitalized for Pertussis [2]. Clearly, Pertussis is a serious disease, especially in the more susceptible populations of infants and the elderly.
Because Pertussis continues to be a major cause of death in children and the elderly, research should be conducted to create a better vaccine for preventing the disease. The current vaccine has a high success rate in children, only if numerous booster shots are given, and about a 70% success rate that fades until a booster is given in adolescents and adults [1]. It is difficult enough for many people in developing countries to get the first Pertussis vaccine, so it is even more difficult for them to obtain the booster vaccine. Research should be conducted to create a vaccine that is not only more accessible to developing countries, but more effective and not requiring a booster shot.
The disease is mainly spread through coughing and sneezing, and being highly contagious, the vaccine against pertussis cannot be 100% effective, but research should be done to improve its effectiveness [1]. Symptoms usually do not appear until five to ten days after contracting the bacteria and people are most contagious two weeks after contracting [1]. The main symptom is severe coughing, however, other common-cold symptoms (runny nose, fever) appear, and symptoms like breathing problems (apnea) also appear, followed by vomiting and exhaustion due to coughing fits [1]. Pertussis is most dangerous for babies because it can often go undiagnosed until the baby suffers severe breathing problems and begins turning blue [1]. Complications of Pertussis in babies includes pneumonia, seizures, apnea, brain damage due to a lack of oxygen, and death [1]. Complications in adolescents and adults tend to be less severe and common, and include weight loss, bladder control problems, fainting, and rib fractures from severe coughing fits [1].
Early treatment is very important in treating Pertussis to the highly contagious nature of the disease. Macrolides such as Erythromycin, clarithromycin and azithromycin are the drugs of choice for treating Pertussis [3]. Research should be done to find other antibiotics in treating Pertussis that may have less side effects and more convenient dosing schedules.Due to the lack of clinical trials in Pertussis, research should go in finding more effective antibiotics and earlier detection methods for Pertussis. Finally, research should be done on discovering drugs that will tend to the serious symptoms of Pertussis.
References: [1] N/A. Pertussis. Centers for Disease Control and Prevention, http://www.cdc.gov/pertussis/about/causes-transmission.html (accessed Feb 4, 2016). [2] Kent, A.; Heath, P. T. Pertussis. Medicine. 2014, 42, 8–10. [3] Spector, T. B.; Maziarz, E. K. Pertussis. Medical Clinics of North America. 2013, 97, 537–552. [4] N/A. Macrolide Antibiotics Comparison. Compare Macrolide Antibiotics: Erythromycin, Clarithromycin, Azithromycin, http://www.emedexpert.com/compare/macrolides.shtml (accessed Feb 6, 2016). [5] Craig-Mylius, K. A.; Weiss, A. A. Antibacterial Agents And Release of Periplasmic Pertussis Toxin from Bordetella Pertussis. Antimicrobial Agents and Chemotherapy. 2000, 44, 1383–1386. [6] Erythromycin. Erythromycin, http://pubchem.ncbi.nlm.nih.gov/compound/12560#section=top (accessed Feb 6, 2016). [7] 50S ribosomal protein L2. rplB, http://www.uniprot.org/uniprot/q7vtd0 (accessed Feb 6, 2016).
Erythromycin inhibits protein synthesis by attaching to the subunits of the 50S ribosome and stopping RNA-based protein synthesis through the dissociation of peptidyl transfer RNA from the ribosome during elongation [4, 5]. Ergo, bacterial growth is inhibited and the release of pertussis toxins occurs at faster than average rates [4, 5].
Figure 2: Model of how antibiotic erythromycin inhibits protein synthesis by attaching to the subunits of the 50S ribosome and stopping RNA-based protein synthesis through the dissociation of peptidyl transfer RNA from the ribosome during elongation.
Size:
A single ribosomal subunit has a mass of about 30, 189 Daltons [7].
Location:
The 50S ribosomal units are generally located in the polypeptide exit tunnels of the bacterial cell.
Function in a normal cell:
The 50S ribosomal units are crucial for forming the 70S ribosome, and for tRNA to bond and create a peptide bond [6, 7].
Drug Information: Erythromycin
Schematic figure of drug:
Figure 3: Schematic structure of erythromycin (C37H67NO13)
Formula: C37H67NO13
Molecular weight: 733.92678 g/mol
CAS Number: 114-07-8
Delivery method: Erythromycin comes in pill form and its dosage is 500 mg, 4 times a day for two weeks.
Side effects: The most common side effects associated with this drug are gastrointestinal symptoms such as vomiting, nausea, abdominal pain, and diarrhea [4]. A very adverse but not common reaction to erythromycin is ototoxicity, which shows up us as tinnitus or deafness [6]
Other names: Erythromycin is commonly known by its own name but has fourteen total different synonym names, with the most common ones being Erythromycin A, Erythromycin C, and Ilotycin [6]
Maker or company: Fourteen versions of the drug are out in the market according to the Food and Drug Administration Orange Book, with many different makers or companies producing the drug [6].
Is it patented? The patent for this drug has long ended, and Erythromycin is available as an inexpensive generic on the market
Clinical Trials Info: According to the government website, no clinical trials have been conducted for Erythromycin in treating Pertussis
Origin: Erythromycin (molecular formula: C37H67NO13) was discovered in 1952, when it was isolated from products made by Streptomyces eythreus [4, 6]
Alternatives to this drug: Although Erythromycin and the newer macrolides Azithromycin and Clarithromycin are equally effective, the latter two are generally preferred in comparison to Erythromycin due to easier dosing schedules and less adverse side effects [3]. Particularly, because Erythromycin is associated with hypertrophic pyloric stenosis in infants under one, Azithromycin is preferred for this age group [3]. Likewise, Azithromycin is also preferred for patients taking multiple medicines due it having fewer drug interactions [3]. Additionally, if one has a resistance or allergy to macrolides, Trimethoprim-sulfamethoxazole can be used as an alternative antibiotic for Pertussis
Miscellaneous: While all macrolides share similar properties and all three can work in the treatment of Pertussis, erythromycin, an antimicrobial drug, is the first macrolide used in treating Pertussis, and therefore, has the most research on it.
Other uses: can this drug be used to treat other diseases/conditions? Erythromycin is a drug with many other uses aside from treating Pertussis, including Streptococcus infections, bacterial pneumonia, infections caused by Chlamydia, and more [4].
Disease/Drug of interest: Bordetella Pertussis - Erythromycin
Motivation and Background:
Pertussis, commonly known as Whooping Cough, is a highly infectious respiratory disease caused by the gram-negative bacteria Bordetella pertussis [2]. Pertussis is categorized by uncontrollable, severe, and chronic coughing which can cause breathing problems in those affected [1]. Due to breathing difficulties, someone infected with Pertussis usually needs to take deep breaths which create a “whooping” sound, leading to the household name “Whooping Cough” [1]. Mainly a concern in children, Pertussis rates have declined in children since the invention of its vaccine in the 1940s [3]. Although the vaccine for Pertussis has saved many lives, Pertussis is still a major cause of vaccine-preventable death, with 30 to 50 million cases per year and 195,000 infant (children younger than 1) deaths worldwide [2, 3]. Ninety percent of these cases appear in developing countries where vaccination rates are lower [3]. Furthermore, in recent years, incidences in older populations has significantly rose, leading to many countries adapting booster vaccines for Pertussis [2]. Adults also act as reservoirs for the bacteria to spread and attack younger children, who are more susceptible to serious side effects of Pertussis, including death [3]. The elderly population also has a 30% fatality rate after being hospitalized for Pertussis [2]. Clearly, Pertussis is a serious disease, especially in the more susceptible populations of infants and the elderly.
Because Pertussis continues to be a major cause of death in children and the elderly, research should be conducted to create a better vaccine for preventing the disease. The current vaccine has a high success rate in children, only if numerous booster shots are given, and about a 70% success rate that fades until a booster is given in adolescents and adults [1]. It is difficult enough for many people in developing countries to get the first Pertussis vaccine, so it is even more difficult for them to obtain the booster vaccine. Research should be conducted to create a vaccine that is not only more accessible to developing countries, but more effective and not requiring a booster shot.
The disease is mainly spread through coughing and sneezing, and being highly contagious, the vaccine against pertussis cannot be 100% effective, but research should be done to improve its effectiveness [1]. Symptoms usually do not appear until five to ten days after contracting the bacteria and people are most contagious two weeks after contracting [1]. The main symptom is severe coughing, however, other common-cold symptoms (runny nose, fever) appear, and symptoms like breathing problems (apnea) also appear, followed by vomiting and exhaustion due to coughing fits [1]. Pertussis is most dangerous for babies because it can often go undiagnosed until the baby suffers severe breathing problems and begins turning blue [1]. Complications of Pertussis in babies includes pneumonia, seizures, apnea, brain damage due to a lack of oxygen, and death [1]. Complications in adolescents and adults tend to be less severe and common, and include weight loss, bladder control problems, fainting, and rib fractures from severe coughing fits [1].
Early treatment is very important in treating Pertussis to the highly contagious nature of the disease. Macrolides such as Erythromycin, clarithromycin and azithromycin are the drugs of choice for treating Pertussis [3]. Research should be done to find other antibiotics in treating Pertussis that may have less side effects and more convenient dosing schedules.Due to the lack of clinical trials in Pertussis, research should go in finding more effective antibiotics and earlier detection methods for Pertussis. Finally, research should be done on discovering drugs that will tend to the serious symptoms of Pertussis.
References:
[1] N/A. Pertussis. Centers for Disease Control and Prevention, http://www.cdc.gov/pertussis/about/causes-transmission.html (accessed Feb 4, 2016).
[2] Kent, A.; Heath, P. T. Pertussis. Medicine. 2014, 42, 8–10.
[3] Spector, T. B.; Maziarz, E. K. Pertussis. Medical Clinics of North America. 2013, 97, 537–552.
[4] N/A. Macrolide Antibiotics Comparison. Compare Macrolide Antibiotics: Erythromycin, Clarithromycin, Azithromycin, http://www.emedexpert.com/compare/macrolides.shtml (accessed Feb 6, 2016).
[5] Craig-Mylius, K. A.; Weiss, A. A. Antibacterial Agents And Release of Periplasmic Pertussis Toxin from Bordetella Pertussis. Antimicrobial Agents and Chemotherapy. 2000, 44, 1383–1386.
[6] Erythromycin. Erythromycin, http://pubchem.ncbi.nlm.nih.gov/compound/12560#section=top (accessed Feb 6, 2016).
[7] 50S ribosomal protein L2. rplB, http://www.uniprot.org/uniprot/q7vtd0 (accessed Feb 6, 2016).
External links:
http://www.cdc.gov/pertussis/about/causes-transmission.htmlhttp://pubchem.ncbi.nlm.nih.gov/compound/12560#section=top
Target Information:
Erythromycin inhibits protein synthesis by attaching to the subunits of the 50S ribosome and stopping RNA-based protein synthesis through the dissociation of peptidyl transfer RNA from the ribosome during elongation [4, 5]. Ergo, bacterial growth is inhibited and the release of pertussis toxins occurs at faster than average rates [4, 5].Size:
A single ribosomal subunit has a mass of about 30, 189 Daltons [7].Location:
The 50S ribosomal units are generally located in the polypeptide exit tunnels of the bacterial cell.Function in a normal cell:
The 50S ribosomal units are crucial for forming the 70S ribosome, and for tRNA to bond and create a peptide bond [6, 7].Drug Information: Erythromycin
Schematic figure of drug:
Formula: C37H67NO13
Molecular weight: 733.92678 g/mol
CAS Number: 114-07-8
Delivery method: Erythromycin comes in pill form and its dosage is 500 mg, 4 times a day for two weeks.
Side effects: The most common side effects associated with this drug are gastrointestinal symptoms such as vomiting, nausea, abdominal pain, and diarrhea [4]. A very adverse but not common reaction to erythromycin is ototoxicity, which shows up us as tinnitus or deafness [6]
Other names: Erythromycin is commonly known by its own name but has fourteen total different synonym names, with the most common ones being Erythromycin A, Erythromycin C, and Ilotycin [6]
Maker or company: Fourteen versions of the drug are out in the market according to the Food and Drug Administration Orange Book, with many different makers or companies producing the drug [6].
Is it patented? The patent for this drug has long ended, and Erythromycin is available as an inexpensive generic on the market
Clinical Trials Info: According to the government website, no clinical trials have been conducted for Erythromycin in treating Pertussis
Origin:
Erythromycin (molecular formula: C37H67NO13) was discovered in 1952, when it was isolated from products made by Streptomyces eythreus [4, 6]
Alternatives to this drug: Although Erythromycin and the newer macrolides Azithromycin and Clarithromycin are equally effective, the latter two are generally preferred in comparison to Erythromycin due to easier dosing schedules and less adverse side effects [3]. Particularly, because Erythromycin is associated with hypertrophic pyloric stenosis in infants under one, Azithromycin is preferred for this age group [3]. Likewise, Azithromycin is also preferred for patients taking multiple medicines due it having fewer drug interactions [3]. Additionally, if one has a resistance or allergy to macrolides, Trimethoprim-sulfamethoxazole can be used as an alternative antibiotic for Pertussis
Miscellaneous:
While all macrolides share similar properties and all three can work in the treatment of Pertussis, erythromycin, an antimicrobial drug, is the first macrolide used in treating Pertussis, and therefore, has the most research on it.
Other uses: can this drug be used to treat other diseases/conditions?
Erythromycin is a drug with many other uses aside from treating Pertussis, including Streptococcus infections, bacterial pneumonia, infections caused by Chlamydia, and more [4].